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  • 1
    ISSN: 1432-5233
    Keywords: Type I diabetes mellitus ; Human recombinant growth hormone ; Insulin-like growth factor I ; Residual beta-cell activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A=21–30 years; B=31–40 years; C=41–50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 282 (1979), S. 11-12 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE German Wool Research Institute houses some of the foremost peptide chemists in the world who sharpen their teeth on insulin as a simple chemical model for the more complicated molecules that will be keeping us warm in the months to come. At the Institute two young students, Peter Thamm and ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Iodoinsulin ; insulin metabolism ; insulin analogues ; biological activity ; tracer insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; insulin-dependent ; glucose recycling ; glucose ; insulin ; Cori cycle ; isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-14C-glucose and 3-3H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69±0.23 to 1.11±0.21 mmol/l (mean±SEM, p〈0.05), total ketones from 0.27±0.06 to 2.06±0.51 mmol/l (p〈0.01), cortisol from 341±43 to 479±31 nmol/l (p〈0.05) and growth hormone from 1.1±0.3 to 19+5-mu/l (p〈0.05). Glucose turnover rose from 13.8±2.3 μmol·kg−1·min−1 at a glucose of 6.9±0.7 mmol/l in the insulin infused study to 25.8±4.4 μmol·kg−1·min−1 (p〈0.05) at a glucose of 16.4±0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0±0.4 μmol· kg−1·min−1 to 9.4±2.2 μmol·kg−1·min−1 (p〈0.05) when insulin withdrawn, accounting for 23±3% and 36±3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Chronic (maturity onset) diabetes mellitus ; glucose tolerance ; insulin and growth hormone secretion ; intermediary metabolites ; lipids ; diet treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-five freshly presenting, diabetic patients received 5 hour, 100 g oral glucose tolerance tests when first seen and after a period of carbohydrate and energy restriction. After treatment, the significant improvement in glucose tolerance was accompanied by increased insulin secretion and lower concentrations of blood ketone bodies, lactate, glycerol, FFA, triglycerides, cholesterol and pre-beta lipoprotein. There were no significant changes in serum growth hormone or blood pyruvate concentrations. Improvement in glucose tolerance was greater in patients who were obese (〉115% of desirable body weight for height) on presentation and was related to the improvement in insulin secretion and the diminished lipolysis. An hypothesis to explain the changes in insulin secretion is proposed. Eleven out of the 35 patients showed sufficient improvement in glucose tolerance to require no treatment other than diet.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 94-101 
    ISSN: 1432-0428
    Keywords: Chemically modified insulins ; gluconeogenesis ; glucose turnover ; insulin structure-function ; proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A [14C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A1 B29-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A1-B29 crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Non insulin dependent diabetes ; sulphonylurea therapy ; chlorpropamide ; glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty diabetic patients, whose hyperglycaemia had been shown to fail to respond to at least one month's dietary treatment, completed a crossover study in order to: 1) compare the effectiveness of two sulphonylureas, chlorpropamide and glibenclamide, and 2) study the effects of sulphonylureas on insulin secretion and on biochemical indices of glucose intolerance. Fasting blood glucose fell on active treatment from 10.7±0.6 (mean ± SEM) to 6.6±0.7 mmol/l and rose again to 10.6±0.7 after 4 months placebo. A second period of 4 months sulphonylurea therapy resulted in a comparable fall in blood glucose (to 6.9±0.7 mmol/l) and a similar relapse was seen after the second placebo period (to 10.5±0.9 mmol/l). Glucose tolerance and associated insulin secretion improved markedly on active treatment, with ketone bodies, non-esterified fatty acids, and glycerol falling to within the reference range. Sulphonylurea therapy was associated with a small but significant increase in the fasting insulin level. These effects were nearly all reversed 4 months after withdrawal of the sulphonylureas. No marked changes were found in growth hormone, lactate, pyruvate, lactate/pyruvate ratio or fasting cholesterol, triglycerides and lipoproteins. On a weight basis, glibenclamide was 26 times more potent than chlorpropamide and, in the doses used in this study, their biochemical effects were indistinguishable. The effects of these two sulphonylureas seem most likely to be mediated by a direct stimulation of insulin secretion by the B-cell.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 27 (1984), S. 207-211 
    ISSN: 1432-0428
    Keywords: Insulin binding ; insulin metabolism ; receptor ; compartmental analysis ; degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A simple model of the distribution and metabolism of insulin in vivo has been evaluated using data from insulin infusion into a group of normal subjects. The major rate-limiting step for access to degradation pathways is assumed to consist of binding of the ligand to a single population of insulin receptor sites, except that provision is made for the possibility of linear non-receptor-mediated degradation and for the phenomenon of negative cooperativity. The model has been shown to accommodate the non-linearity of insulin metabo lism, allows evaluation of receptor association and dissociation constants and provides for the first time an estimate of total accessible receptor number in the intact organism. For normal fasting man the model predicts 1.00±0.05 nmol accessible binding sites/kg (mean±SD).
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Gestational diabetes ; glucose metabolism ; insulin secretion ; intravenous glucose tolerance test ; minimal model ; pregnancy ; stable isotope.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gestational diabetes affects 2–3 % of pregnant women and is associated with foetal complications including macrosomia and an increased likelihood of developing diabetes in later life. We have therefore studied seven women with gestational diabetes and five control women both during the third trimester of pregnancy and again 2–3 months post-partum, using the minimal model analysis of the frequently sampled labelled ([6, 6-2H2]-glucose) intravenous glucose tolerance test. Glucose tolerance (glucose Kd) was significantly reduced in the women with gestational diabetes compared with the normal pregnant women both in pregnancy (1.16 ± 0.11 vs 1.78 ± 0.23 %/min; p 〈 0.05) and post-partum (1.47 ± 0.22 vs 2.59 ± 0.43 %/min; p 〈 0.05) and increased significantly in the control women after delivery (p 〈 0.05). Glucose effectiveness was not significantly different between the women with gestational diabetes and the control group either during or after pregnancy. Insulin sensitivity was significantly lower during pregnancy than after delivery in the women with gestational diabetes (p 〈 0.05). There was no significant difference in basal insulin secretion in the two groups during pregnancy or post-partum. However, during pregnancy the control subjects significantly increased (p 〈 0.001) their insulin secretion over a period of 20 min in response to an intravenous glucose tolerance test (96.2 ± 42.7 pmol/kg) compared with post-partum values (58.3 ± 25.2 pmol/kg) while in the women with gestational diabetes insulin secretion was similar in pregnancy (65.5 ± 9.3 pmol/kg) and after delivery (57.7 ± 15.7 pmol/kg). These data suggest that the glucose intolerance in gestational diabetes compared to normal pregnancy is due to reduced insulin sensitivity and an impaired ability in gestational diabetes to increase insulin secretion in response to glucose. [Diabetologia (1996) 39: 976–983]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Insulin structure-function ; chemically modified insulin ; proinsulin ; bioactivity of insulin analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Beef insulin, pork proinsulin and four derivatives of beef insulin modified at the A1-B29 site on the molecular surface have been studied. Three derivatives had a synthetic crosslink between the A and B chains. Previous studies with these materials [2, 3 and 5] had demonstrated in vivo bioactivities which were much higher than those displayed in vitro. This paper reports experiments which explain this discrepancy. The analogues were administered at equimolar rates to anaesthetised greyhounds by a priming-dose constant infusion technique and the plasma concentrations achieved were estimated by radioimmunoassay. Proinsulin and the modified insulins were metabolised more slowly than insulin. Biopotency values, which related fall in plasma glucose concentration to the total administered dose of analogue, agreed broadly with published results of conventional in vivo bioassays. On the other hand, calculation of potency in relation to the serum concentration of analogue actually achieved, yielded results which agreed more closely with in vitro assay data. We conclude that for these analogues, reported discrepancies between in vitro and in vivo biopotencies can be largely explained by the different rates at which these materials are metabolised.
    Type of Medium: Electronic Resource
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